1. Field of the invention
The present invention relates to a method for inhibiting a neuronal cell death induced by oxidative glutamate toxicity.
2. Discussion of the Background
Resistance to oxidative stress often determines neuronal survival in the brain. Thus, antioxidants appear to be promising neuroprotective compounds against neurodegenerative diseases. For example, N,N′-diphenyl-p-phenylenediamine (DPPD) reportedly exerts cytoprotective effects against oxidative stress, possibly by acting as an antioxidant. DPPD provides hydrogen thereby scavenging free radicals, and protects cells from oxidative stress. However, there is no critical biological evidence to show that its antioxidant ability actually prevents cell death.
Oxidative stress, defined as the accumulation of reactive oxygen species (ROS) caused by enhancement of ROS production or by suppression of ROS destruction, plays a pivotal role in neurodegeneration associated with ischemia, trauma, and other neurodegenerative diseases [1-4]. The accumulation of ROS in neurons results in lipid peroxidation, protein oxidation, DNA damage, and finally cell death [1-4]. Thus, antioxidants are one of the potential targets of drug development for neuroprotection [2-3]. Basically, antioxidants are categorized into two distinctive groups: 1) hydrophilic and 2) lipophilic ones. Hydrophilic antioxidants, such as vitamin C or glutathione, are believed to react with water-soluble ROSs (superoxide anion [O2-], or hydrogen peroxide [H2O2]). In contrast, lipophilic antioxidants are believed to suppress lipid peroxidation. Two of the latter, vitamin E and N,N′-diphenyl-p-phenylenediamine (DPPD, FIG. 1) are believed to become inserted into the cell membrane and maintain membrane integrity, thereby providing potent cytoprotective actions against oxidative stress [1]. In vivo, DPPD protected animals against various insults initiated by oxidative stress resulting from brain or renal ischemia or carbon tetrachloride treatment [5-7]. Also, DPPD exerted a cytoprotective effects in vitro against oxidative stress on various types of cells including neuronal cell lines PC12 and HT22 [8-15]. For example, DPPD at μM concentrations protected PC12 cells against lipid peroxide, which protection was associated with a decrease in intracellular ROS levels [13]. These results suggest that DPPD protects neuronal cells against oxidative stress by acting as an antioxidant in both in vivo and in vitro systems [5-15].
There exists a need for methods of substantially inhibiting a neuronal cell death induced by an oxidative glutamate toxicity.